Emulsified fatty acids

ABSTRACT

Provided herein are methods and processes for emulsifying non-polar compounds, such as omega fatty acids. Also provided are compositions that can be prepared according to the methods and processes described herein. The compositions, for example, have a high amount of the non-polar compound, such as a large amount of omega fatty acids. The non-polar compounds are also present in very small droplets within composition. For example, the mean or median particle size of the droplets is less than about 5 μm. Further, the composition includes a low amount of surfactant, such as less than about 10-15% of the surfactant.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/151,039, filed Oct. 3, 2018, which is a continuation of U.S. patentapplication Ser. No. 15/847,736, filed Dec. 19, 2017, now U.S. Pat. No.10,117,832, issued Nov. 6, 2018, which claims benefit of priority toU.S. Provisional Application No. 62/572,275, filed Oct. 13, 2017, titled“Emulsified Fatty Acids,” and to U.S. Provisional Application No.62/436,634, filed Dec. 20, 2016, titled “Emulsified Fatty Acids.” Theentire disclosures of the above-identified priority applications arehereby fully incorporated herein by reference.

TECHNICAL FIELD

The present invention relates generally to methods for emulsifying fattyacids, and more particularly to methods of making emulsified fatty acidcompositions having a high percentage of fatty acid, the fatty acidsbeing present in droplets with a reduced particle size.

BACKGROUND

Consumption of omega fatty acids are associated with numerous healthbenefits. A diet rich in omega-3 fatty acids, for example, is associatedwith lowered elevated blood triglyceride levels and hence a reduced riskof heart disease. An omega-3-rich diet is also associated with animproved blood glucose, a reduced risk of obesity, improved cognitivefunction, among several other benefits. As for omega-7 fatty acids, ithas been suggested that this fatty acid can reduce high cholesterol andtriglyceride levels, thus improving cardiovascular health. Consumptionof omega-7 fatty acids has also been implicated in lowering insulinlevels, improving liver function, and promoting weight loss. Omega-5fatty acids have been shown to act a potent anti-oxidant, and are alsobelieved to have anti-inflammatory properties. Omega-6 fatty acids havebeen implicated in playing an important role in brain function, andnormal growth and development. Omega-6 fatty acids may also maintainbone health, regulate metabolism, and maintain a healthy reproductivesystem.

While the benefits of omega fatty acids are well recognized, providingreadily-absorbable fatty acid products has proven challenging. This isdue largely to the fact that non-polar compounds, such as fatty acids,are not easily dissolved in polar solutions such as water. Conventionalemulsification processes, for example, often result in the coalescenceof fatty acids into large droplets that are associated with poorbioavailability following consumption. Further, to reduce particle sizeof the droplets, large amounts of surfactants and/or solubilizing agentsare often needed, thus increasing production costs and reducing theproportion of fatty acids that are ultimately present in the finishedproduct. Surfactants and co-surfactants, for example, also haveundesirable side-effects, and hence their use is disadvantageous orprohibitive in many applications. And even with the use of large amountsof surfactants and/or solubilizing agents, the particle sizes of thefatty acid droplets often remain larger than desired in the finishedproduct, thus impacting bioavailability of the fatty acids whenconsumed.

Hence, what is needed is a cost-effective emulsification process thatresults in a final product having a high level of fatty acids. Inaddition to a high level of fatty acids, what is needed is a compositionin which the emulsified droplets of the fatty acids have a small size,thus improving absorption when the emulsion is consumed. Also needed areemulsification processes that result in a small fatty-acid droplet sizebut yet do not rely on large amounts of solubilizing agents and/orsurfactants.

SUMMARY

In certain example aspects, provided is a method for providing anemulsion. The method includes providing a first mixture, the firstmixture including less than about 15% by weight of d-α-tocopherylpolyethylene glycol 1000 succinate (“TPGS”) or derivative thereof. Themixture also includes a non-polar compound or mixture of non-polarcompounds. The method also includes providing a second mixture, thesecond mixture including water and one or more emulsifiers. The one ormore emulsifiers are, for example, less than about 15% of the secondmixture. The method further includes combining the first mixture withthe second mixture under high shear to form an emulsion of the non-polarcompound or mixture of non-polar compounds. The non-polar compounds ormixture thereof are present, for example, in droplets having a particlesize of about 5 μm or less and the non-polar compounds or mixturethereof comprise at least about 20% by weight of the emulsification.

In certain other example aspects, provided is a process for forming anemulsion. A lipid component is combined with an aqueous component(aqueous phase) under high shear mixing. The lipid component includesless than about 15% by weight of TPGS or derivatives thereof, and atleast one or more non-polar compounds, such as an omega fatty acid. Theaqueous component includes less that about 15% by weight of one or moreemulsifiers, with the balance of the aqueous component being one or morecarriers. The emulsion resulting from the combination of the lipidcomponent and the aqueous component under high shear mixing includes atleast about 20% by weight of the one or more non-polar compounds.Further, the emulsion includes droplets of the lipid component, thedroplets having a particle size less than or equal to about 5 μm.

In certain example aspects, the non-polar compounds or mixture thereofare at least about 30% by weight of the emulsification and the TPGS isless than about 5% by weight of the emulsification. In certain exampleaspects, the non-polar compound or mixture thereof includes a fattyacid, such as an omega fatty acid. For example, the omega fatty acid canbe an omega-3 fatty acid, an omega-5 fatty acid, an omega-6 fatty acid,an omega-7 fatty acid, or a mixture thereof.

In certain other example aspects, provided is an emulsion composition,such as an emulsion composition made according to the methods andprocesses for forming an emulsion described herein. The emulsion, forexample, includes at least about 20% by weight of the one or morenon-polar compounds, such at least about 20% by weight of omega fattyacids. The composition also includes less than about 15% by weight ofthe TPGS. The composition further includes droplets of the non-polarcompounds having a particle size less than or equal to 5 μm.

In certain example aspects, the emulsion can further include a weakacid, such as citric acid, ascorbic acid, malic acid, or a combinationthereof. In certain example aspects, the emulsion further comprisesabout 1-20% by weight glycerine. In certain example aspects, theemulsion further comprises xylitol, erythritol, or a combinationthereof. In certain example aspects, the emulsion further comprises 1-5%by weight tocopherol and rosemary extract. In certain example aspects,the emulsion further comprises a preservative such as sorbic acid,potassium sorbate, sodium benzoate, or combination thereof.

In certain example aspects, provided is an emulsified lipid composition.The composition includes an emulsifier that is less than about 10% byweight of the composition. The composition also includes a surfactantthat is less than about 10% by weight of the composition. Thecomposition also includes one or more lipid compounds, the one or morelipids being at least about 20% by weight of the composition. Further,the one or more lipid compounds are present in emulsified droplets, theemulsified droplets having a particle size of about 5 μm or less.

These illustrative features are mentioned not to limit or define thedisclosure, but to provide examples to aid understanding thereof.Additional embodiments are discussed in the Detailed Description, andfurther description is provided there.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is graph showing a differential histogram of particle sizedistribution for a sample in which 14.7% TPGS was used in the premix, inaccordance with certain example embodiments. The resultant final productcontained 29% non-polar component (oil) and 5% TPGS. The mean non-polar(oil) component particle size was 0.713 μm for the final product.

FIG. 2 is graph showing a differential histogram of particle sizedistribution for a sample in which 9.41% TPGS was used in the premix, inaccordance with certain example embodiments. The resultant final productcontained 28.88% non-polar component (oil) and 3% TPGS. The meannon-polar (oil) component particle size was 1.019 μm for the finalproduct.

FIG. 3 is graph showing a differential histogram of particle sizedistribution for a sample in which 3.35% TPGS was used in the premix, inaccordance with certain example embodiments. The resultant final productcontained 28.88% non-polar component (oil) and 1.0% TPGS. The meannon-polar (oil) component particle size was 1.753 μm for the finalproduct.

FIG. 4 is graph showing a differential histogram of particle sizedistribution for a sample in which 2.13% TPGS was used in the premix, inaccordance with certain example embodiments. The resultant final productcontained 23% non-polar component (oil) and 0.5% TPGS. The meannon-polar (oil) component particle size was 2.570 μm for the finalproduct.

FIG. 5 is graph showing a differential histogram of particle sizedistribution for a sample in which 1.35% TPGS was used in the premix, inaccordance with certain example embodiments. The resultant final productcontained 22.8% non-polar component (oil) and 0.3% TPGS. The meannon-polar (oil) component particle size was 2.226 μm for the finalproduct.

FIG. 6 is graph showing a differential histogram of particle sizedistribution for a sample in which TPGS was not included in the premix,in accordance with certain example embodiments. The resultant finalproduct contained 38% non-polar component (oil). As shown, however, themean non-polar (oil) component particle size was 7.470 μm for the finalproduct.

DETAILED DESCRIPTION OF THE EXAMPLE EMBODIMENTS

The embodiments described herein can be understood more readily byreference to the following detailed description, examples, and claims,and their previous and following description. Before the present system,devices, compositions and/or methods are disclosed and described, it isto be understood that the embodiments described herein are not limitedto the specific systems, devices, and/or compositions methods disclosedunless otherwise specified, as such can, of course, vary. It is also tobe understood that the terminology used herein is for the purpose ofdescribing particular aspects only and is not intended to be limiting.

Further, the following description is provided as an enabling teachingof the various embodiments in their best, currently known aspect. Thoseskilled in the relevant art will recognize that many changes can be madeto the aspects described, while still obtaining the beneficial resultsof this disclosure. It will also be apparent that some of the desiredbenefits of the present invention can be obtained by selecting some ofthe features of the various embodiments without utilizing otherfeatures. Accordingly, those who work in the art will recognize thatmany modifications and adaptations to the various embodiments describedherein are possible and can even be desirable in certain circumstancesand are a part of the present disclosure. Thus, the followingdescription is provided as illustrative of the principles of theembodiments described herein and not in limitation thereof.

Overview

As described herein, provided are methods and processes for emulsifyingnon-polar compounds, such as omega fatty acids. Also provided arecompositions that can be prepared according to the methods and processesdescribe herein. The compositions, for example, have a high amount ofthe non-polar compound, such as a large amount of omega fatty acids. Thenon-polar compounds are also present in very small droplets withincomposition. Further, the composition includes a low amount ofsurfactant.

More particularly, in certain examples the methods and process involvepreparing a first mixture, the first mixture being a lipid component.The lipid component includes, for example, a large amount of non-polarcompound or a mixture of non-polar compounds, such as a large amount ofone or more fatty acids. In certain examples, the fatty acids are omegafatty acids. The lipid component also includes a low amount of asurfactant. In certain examples, the surfactant is d-α-tocopherylpolyethylene glycol 1000 succinate (TPGS) or a derivative thereof. TPGSis a tasteless and odorless, water-soluble form of Vitamin E, which theFood & Drug Administration has approved as vitamin E nutritionalsupplement. TPGS is also functions as an emulsion stabilizer.

Upon mixing the TPGS or derivate thereof with the non-polar compounds, aliquid premix is formed as a lipid component. While a co-surfactant maybe added to the lipid component, the first mixture can be free oressentially free of any co-surfactant, as such co-surfactants ultimatelyreduce the total proportion of non-polar compounds. For example, suchco-surfactants reduce the proportion of fatty acids that can be presentin the final emulsified product.

In addition to the first mixture, a second mixture is prepared, thesecond mixture being an aqueous component. The aqueous componentincludes, for example, an emulsifier or mixture of emulsifiers oremulsion stabilizers that are mixed with a carrier. The carrier, forexample, can be water or any other polar solution that is suitable forconsumption. In certain examples, water can be mixed with another polarcompound to form the carrier. Further, a variety of emulsifiers may beused, including a modified starch or gum mixtures such as gum arabic,xanthan gum, guar gum, modified gum acacia, and/or an ester gum.

Once the aqueous component (second mixture) is formed, the lipidcomponent (first mixture) is slowly added to the aqueous component underhigh shear mixing conditions. The lipid component is slowly added untilthe desired amount of lipid component has been mixed with the aqueouscomponent. The high shear mixing, for example, homogenizes the twocomponents into an oil-in-water-type emulsion, with the “oil” portionbeing the non-polar compounds, such as omega fatty acids.

In certain examples, various other additives and components may be addedto the emulsion. For example, other components may be added duringpreparation of the aqueous component and/or during the mixing of thelipid phase with the aqueous phase. Such components include, forexample, flavorings, sweeteners, colorings, preservatives, stabilizers,humectants, pH adjusters, antioxidants, and/or other additives.

The emulsion made according to the methods and processes describedherein is also a microemulsion, inasmuch as the emulsified droplets ofnon-polar compounds have a particle size, such as a mean or medianparticle size, in the micrometer range, such as about 10 μm or less oreven 5 μm or less. Further, because of the low amount of surfactant usedto prepare the lipid component, the emulsion has a very low amount ofsurfactant. Yet because of the large amount of non-polar compounds addedto the lipid phase, the emulsion still has a large amount of thenon-polar compound, such as a large amount of omega fatty acids. Forexample, the emulsion can contain from about 20% to about 80% by weightfatty acids, with less than 5-10% surfactant.

Summary of Terms

The invention will now be described in detail by way of reference onlyusing the following definitions and examples. Unless defined otherwiseherein, all technical and scientific terms used herein have the samemeaning as commonly understood by one of ordinary skill in the art towhich this invention belongs. Although any methods and materials similaror equivalent to those described herein can be used in the practice ortesting of the present invention, the preferred methods and materialsare described. It is to be understood that this invention is not limitedto the particular methodology, protocols, and reagents described, asthese may vary.

The headings provided herein are not limitations of the various aspectsor embodiments of the invention which can be had by reference to thespecification as a whole. Accordingly, the terms defined immediatelybelow are more fully defined by reference to the specification as awhole.

As used herein, the singular forms “a,” “an” and “the” include pluralreferents unless the context clearly dictates otherwise.

Ranges or values can be expressed herein as from “about” one particularvalue, and/or to “about” another particular value. When such a range isexpressed, another aspect includes from the one particular value of therange and/or to the other particular value of the range. It will befurther understood that the endpoints of each of the ranges aresignificant both in relation to the other endpoint, and independently ofthe other endpoint. Similarly, when values are expressed asapproximations, by use of the antecedent “about,” it will be understoodthat the particular value forms another aspect. In certain exampleembodiments, the term “about” is understood as within a range of normaltolerance in the art for a given measurement, for example, such aswithin 2 standard deviations of the mean. In certain exampleembodiments, depending on the measurement “about” can be understood aswithin 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, 1%, 0.5%, 0.1%, 0.05%, or0.01% of the stated value. Unless otherwise clear from context, allnumerical values provided herein can be modified by the term about.Further, terms used herein such as “example,” “exemplary,” or“exemplified,” are not meant to show preference, but rather to explainthat the aspect discussed thereafter is merely one example of the aspectpresented.

As used herein, the term “additive” includes any component that can beadded to foodstuffs or other consumable product to enhance one or moreof its nutritional, pharmaceutical, dietary, health, nutraceutical,pharmaceutical, health benefit, energy-providing, treating, taste,shelf-life, holistic properties, or other properties. Certain additivesthat may be used with the methods and compositions described hereininclude, for example, stabilizers and humectants such as glycerin; pHadjusters such as citric, ascorbic acid, and malic acid; sweeteners suchas xylitol, erythritol, and/or other sugar alcohols; consumableflavoring agents; consumable coloring agents; and, preservatives such assorbic acid, potassium sorbate, sodium benzoate and other naturalantimicrobial derived from fruit which has bioflavonoids and organicacids; essential oils; and fragrances. Other additives known to thoseskilled in the art can also be added based on, for example, the intendeduse of the finished product.

As used herein “tocopherol” refers to the four different forms of theVitamin E family represented by the formula below:

For alpha-tocopherol R and R¹═CH₃, beta-tocopherol R═CH₃ and R¹═H,gamma-tocopherol R═H and R¹═CH₃, and delta-tocopherol R and R¹═H. Eachisomer can be present alone or in combination with the other isomers.

As used herein “tocotrienol” refers to the four different forms of theVitamin E family represented by the formula below.

For alpha-tocotrienol R and R¹═CH₃, beta-tocotrienol R═CH₃ and R¹═H,gamma-tocotrienol R═H and R¹═CH₃, and delta-tocotrienol R and R¹═H. Eachisomer can be present alone or in combination with the other isomers.

Disclosed herein is the use of d-α-tocopheryl polyethylene glycol 1000succinate (TPGS) having the formula:

wherein the index n has an average value of 25.

Disclosed herein are TPGS “derivatives.” The derivatives can vary by thenumber of ethyleneoxy units, for example, n=50, or by substituting atocotrienol unit for the tocopherol.

As used herein, “colloid” refers to a mixture containing two phases, adispersed phase and a continuous phase, the dispersed phase containingparticles (droplets) distributed throughout the continuous phase.Colloidal mixtures include aerosols, foams and dispersions, for example,emulsions, for example, nanoemulsions. A liquid colloid, for example, ananoemulsion, can have a similar appearance, for example, clarity, to asolution in which there is no dispersed phase.

As used herein the term “emulsion” refers to a colloidal dispersion oftwo immiscible liquids, for example, an oil (lipid) in water colloid(O/W), a water in oil colloid (W/O), an oil in water in oil colloid(O/W/O) or a water in oil in water colloid (W/O/W). In the oil in wateremulsion, a hydrophobic phase (oil) is dispersed in an aqueous phase(water). one of which is part of a continuous phase and the other ofwhich is part of a dispersed phase. The provided liquid dilutioncompositions include emulsions, typically oil-in-water nanoemulsions(which include any oil soluble phase dispersed in any aqueous phase,also called the water phase), in which the oil phase is the dispersedphase and the water phase is the continuous phase.

As used herein the term “median particle size” refers to the averagediameter of the droplets that are dispersed in the nonpolar (oil) phaseof the disclosed dispersions. “Particle Size Distribution D50” is alsoknown as the median diameter or the medium value of the particle sizedistribution. This is the value of the particle diameter at 50% in thecumulative distribution. For example, if D50=5.8 μm, then 50% of theparticles in the sample are larger than 5.8 μm, and 50% smaller than 5.8μm. The median particle size and/or the particle size distribution canbe determined by any method chosen by the formulator. In certain exampleembodiments, the particle size may be a “mean” particle size of thedroplets that are dispersed in the nonpolar (oil) phase of the discloseddispersions. For example, the mean particle size may be a volumeweighted mean.

As used herein, the term “high shear,” such as used in the context ofhigh shear mixing, refers to mixing in which a force is used to push apart of an object (such as an oil droplet) in one direction and anotherpart of the object in a different direction (i.e., a shear force). Asthose skilled in the art will appreciate, a high shear mixer typicallyuses a rotor, rotating at high speeds, to direct material outwardstowards a stationary stator, thus shearing the material. Variable rotorspeeds provide the ability to uniquely tailor the amount of shear energyfor each application. High shear mixing can be used for homogenization,dispersion, emulsification or particle size reduction. For example, highshear mixing can be used to disperse oil into water (or other aqueousphase) by shearing the oil droplets into smaller and smaller droplets.

EXAMPLE EMBODIMENTS

In certain example embodiments, disclosed herein is a process forforming an emulsion, comprising combining under high shear mixing:

a) a lipid component comprising:

-   -   i) less than about 15% by weight of d-α-tocopheryl polyethylene        glycol 1000 succinate (TPGS) or derivatives thereof, and    -   ii) at least one or more non-polar compounds; and        b) an aqueous component comprising:    -   i) less that about 15% by weight of one or more emulsifiers, and    -   ii) the balance one or more carriers;        wherein the emulsion comprises at least about 20% by weight of        the one or more non-polar compounds and wherein the emulsion        comprises lipid-component droplets having a median or mean        particle size less than or equal to 5 μm.

In certain example embodiments, provided is a method for providing anemulsion, comprising providing a first mixture, wherein the firstmixture comprises less than about 15% by weight of TPGS or derivativethereof and a non-polar compound or mixture of non-polar compounds. Themethod also includes providing a second mixture, wherein the secondmixture comprises water and one or more emulsifiers and wherein the oneor more emulsifiers comprise less than about 15% of the second mixture.Thereafter, the first mixture can be combined with the second mixtureunder high shear to form an emulsion of the non-polar compound ormixture of non-polar compounds. The non-polar compounds or mixturethereof are present in droplets having a particle size of about 5 μm orless and wherein the non-polar compounds or mixture thereof comprise atleast about 20% by weight of the emulsification.

The droplets formed by the disclosed process and method, also referredto herein interchangeably as “micelles” or “particles” have an averagediameter of less than or equal to 5 μm. In certain example embodimentsthe average diameter is less than or equal to 4.5 μm. In certain exampleembodiments, the average diameter is less than or equal to 4 μm. In afurther embodiment the average diameter is less than or equal to 3.5 μm.In further embodiments the average diameter is less than or equal to 3μm. In a yet another embodiment the average diameter is less than orequal to 2.5 μm. In a still yet further embodiment the average diameteris less than or equal to 2 μm. In a still yet another embodiment theaverage diameter is less than or equal to 1.5 μm. In a yet still furtherembodiment the average diameter is less than or equal to 1 μm. Theaverage diameter can have any value from 5 nanometers (nm) to 5 μm. Theaverage diameter can have any value in the recited range. For example,in the range 5 nm to 100 nm, the average can be any value, i.e., 5 nm, 6nm, 7 nm, 8 nm, 9 nm, 10 nm, 11 nm, 12 nm, 13 nm, 14 nm, 15 nm, 16 nm,17 nm, 18 nm, 19 nm, 20 nm, 21 nm, 22 nm, 23 nm, 24 nm, 25 nm, 26 nm, 27nm, 28 nm, 29 nm, 30 nm, 31 nm, 32 nm, 33 nm, 34 nm, 35 nm, 36 nm, 37nm, 38 nm, 39 nm, 40 nm, 41 nm, 42 nm, 43 nm, 44 nm, 45 nm, 46 nm, 47nm, 48 nm, 49 nm, 50 nm, 55 nm, 52 nm, 53 nm, 54 nm, 55 nm, 56 nm, 57nm, 58 nm, 59 nm, 60 nm, 61 nm, 62 nm, 63 nm, 64 nm, 65 nm, 66 nm, 67nm, 68 nm, 69 nm, 70 nm, 71 nm, 72 nm, 73 nm, 74 nm, 75 nm, 76 nm, 77nm, 78 nm, 79 nm, 80 nm, 81 nm, 82 nm, 83 nm, 84 nm, 85 nm, 86 nm, 87nm, 88 nm, 89 nm, 90 nm, 91 nm, 92 nm, 93 nm, 94 nm, 95 nm, 96 nm, 97nm, 98 nm, 99 nm and 100 nm.

The droplets formed by the disclosed method and process, also referredto herein interchangeably as “micelles” or “particles,” have a particlesize distribution, D50, from about 50 nm to about 5 μm. In oneembodiment the particle size distribution, D50, from about 50 nm toabout 5 μm. In another embodiment the particle size distribution, D50,from about 100 nm to about 5 μm. In a further embodiment the particlesize distribution, D50, from about 100 nm to about 1 μm. In a stillfurther embodiment the particle size distribution, D50, from about 1 μmto about 5 μm. In a yet another embodiment the particle sizedistribution, D50, from about 250 nm to about 1 μm. In a still yetfurther embodiment the particle size distribution, D50, from about 1 μmto about 5 μm. In a still yet another embodiment the particle sizedistribution, D50, from about 500 nm to about 5 μm. In a yet stillfurther embodiment the particle size distribution, D50, from about 500nm to about 1 μm. In yet still further embodiments, the particle sizedistribution, D50, is about 0.3 μm, 0.4 μm, 0.5 μm, 0.6 μm, 0.7 μm, 0.8μm, 0.9 μm, 1.0 μm, 1.5 μm, 2.0 μm, 2.5 μm, 3.0 μm, 3.5 μm, 4.0 μm, 4.5μm, or 5.0 μm.

In certain example embodiments, the particle size distribution, D50, canhave any value from 5 nanometers (nm) to 5 μm in the recited range. Forexample, in the range 50 nm to 1 μm, the average can be any value, i.e.,50 nm, 60 nm, 70 nm, 80 nm, 90 nm, 100 nm, 110 nm, 120 nm, 130 nm, 140nm, 150 nm, 160 nm, 170 nm, 180 nm, 190 nm, 200 nm, 210 nm, 220 nm, 230nm, 240 nm, 250 nm, 260 nm, 270 nm, 280 nm, 290 nm, 300 nm, 310 nm, 320nm, 330 nm, 340 nm, 350 nm, 360 nm, 370 nm, 380 nm, 390 nm, 400 nm, 410nm, 420 nm, 430 nm, 440 nm, 450 nm, 460 nm, 470 nm, 480 nm, 490 nm, 500nm, 550 nm, 520 nm, 530 nm, 540 nm, 550 nm, 560 nm, 570 nm, 580 nm, 590nm, 600 nm, 610 nm, 620 nm, 630 nm, 640 nm, 650 nm, 660 nm, 670 nm, 680nm, 690 nm, 700 nm, 710 nm, 720 nm, 730 nm, 740 nm, 750 nm, 760 nm, 770nm, 780 nm, 790 nm, 800 nm, 810 nm, 820 nm, 830 nm, 840 nm, 850 nm, 860nm, 870 nm, 880 nm, 890 nm, 900 nm, 910 nm, 920 nm, 930 nm, 940 nm, 950nm, 960 nm, 970 nm, 980 nm, 990 nm and 1 μm.

When the average particle size or particle size distribution is in therange of from about 10 nm to about 100 nm the droplets for what isreferred to herein as “nano-emulsions.” The disclosed nano-emulsionscontain micelles and can contain one or more surfactants surrounding anon-polar active ingredient, which is dispersed in the water phase. Thesurfactants are disclosed herein below.

Particle size can be determined by a variety of conventional methods. Incertain example embodiments, Light Amplification by Stimulated Emissionof Radiation using MalvernSize LASER Diffractor (e.g., Model S and Model2000 instruments) can be used to determine particles size.

In certain example embodiments, emulsions are oil-in-water emulsions,i.e., are colloidal dispersions of an immiscible organic phase in anaqueous phase wherein the immiscible organic phase is continuous andequally dispersed. The droplets of the disclosed emulsions can have theaverage particle size or particle size distribution as described herein.

In certain example embodiments of the disclosed process the “at leastone or more non-polar compounds” of section (a)(ii) comprises one ormore “unsaturated fatty acids.” The unsaturated fatty acids can be inthe form of mono-, di- and triglycerides or fatty acid esters, forexample, ethyl esters, or derivatives thereof.

In certain example embodiments of the disclosed method and process thesource of the unsaturated fatty acids is derived from fish oils. Thesource of the fish oils can be from any type of fish, typically “oilyfish” or from algal sources. Non-limiting examples of oily fish includesalmon, herring, mackerel, anchovies and sardines, however, the fish oilcan be obtained from any fish which provides the required profile ofnutritionally important unsaturated fatty acids.

In certain example embodiments of the disclosed method and process, theunsaturated fatty acids can be obtained from vegetable sources, forexample, vegetable oils. Non-limiting examples of vegetable oilsincludes coconut oil, corn oil, cottonseed oil, olive oil, palm oil,peanut oil, canola oil, safflower oil, sesame oil, soybean oil andsunflower oil. Any edible oil, however, including oils obtained fromnuts, can be used as a component of the non-polar compounds in thisembodiment.

In certain example embodiments, an admixture of one or more fish oilsand vegetable oils can be used. In one example, fatty acid mono-, di- ortriglycerides and fatty acid esters easily obtained from vegetable oils,for example, oleic, linolenic and linoleic fatty acids can be added toenhance the amount of “unsaturated fatty acids” that comprise the “atleast one or more non-polar compounds” of section (a)(ii).” Non-limitingexamples of fatty acids derived from fish oil include the omega-3 fattyacids, omega-5 fatty acids, omega-6 fatty acids, omega-7 fatty acids,and mixtures thereof, particularly eicosapentaenoic acid (EPA),docosahexaenoic acid (DHA) and arachidonic acid (AA).

In certain example embodiments of this aspect d-α-tocopherylpolyethylene glycol 1000 succinate (TPGS) is used as the component ofsection (a)(i). In another embodiment, derivatives of TPGS can be usedeither alone or in combination with TPGS or other derivatives.Non-limiting examples of TPGS derivatives includes d-α-tocopherylpolyethylene glycol 2000 succinate (TPGS_(2k)) and d-α-tocopherylpolyethylene glycol 1500 succinate. In certain examples embodiments, theTPGS of the lipid component of the process is less than about 15%, 14%,13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, or 5%. In certain examplesembodiments, the TPGS of the first reaction mixture is less than about15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, or 5%. In certain exampleembodiments, the TPGS comprises less than about 10%, 9%, 8%, 7%, 6%, or5% of the emulsion resulting from the methods and processes describedherein.

As those skilled in the art will appreciate, any high shear mixers knownin the art can be used to achieve the high shear mixing describedherein. Example high shear mixers include those supplied under thebrands “TK Products Homomic Line Mill” or “Bematek” or “Greerco” or“Ross.” Example suppliers include IKA WORKS, Kady International, CharlesRoss and Son Company, Silverson Machines, and Pulsar. A specific mixerthat can be used in accordance with the methods and processes describedherein is the Ross™ HSM-405SC-25 high shear mixer. In certain exampleembodiments, the rotor speed of the mixer is around 3,600 revolutionsper minutes (rpm), such as around 1,400 rpm, 1,600 rpm, 1,800 rpm, 2,000rpm, 2,200 rpm, 2,400 rpm, 2,600 rpm, 2,800 rpm, 3,000 rpm, 3,200 rpm,3,400 rpm, 3,600 rpm, 3,800 rpm, 4,000 rpm, 4,200 rpm, 4,400 rpm, 4,600rpm, 4,800 rpm, 5,000 rpm, 5,200 rpm, 5,400 rpm, 5,600 rpm or higher. Incertain example embodiments, the rotor speed of the mixer is between2,000 rpm to 6,000 rpm. In certain example embodiments, the rotor speedis between 3,000 rpm and 5,000 rpm. In certain example embodiments, therotor speed is between 3,000 rpm and 4,000 rpm. With such high shearmixing, for example, hygroscopic emulsifiers can be mixed into theaqueous phase. Further, the high shear mixing emulsifies the lipid phasewith the aqueous phase to form the final emulsion, in accordance withthe methods and processes provided herein.

Emulsifiers

In the disclosed process the one or more emulsifiers can be chosen fromany emulsifiers that provides the desired median or mean particle sizeof the resulting droplets. One category of emulsifiers includes, forexample, C₁₄-C₂₂ fatty alcohols non-limiting examples of which arechosen from 1-tetradecanol (myristyl alcohol), 1-hexadecanol (cetylalcohol), cis-9-hexadecen-1-ol (plamitoleyl alcohol), 1-octadecanol(stearyl alcohol), cis-9-octadecen-1-ol (oleyl alcohol),trans-9-octadecen-1-ol (elaidyl alcohol), 1-eicosanol (arachidylalcohol), and 1-docosanol (behenyl alcohol). Further non-limitingexamples of emulsifiers include esters of C₁₄-C₂₂ fatty alcohols andinorganic acids chosen from di-1-tetradecanyl phosphate (di-myristylphosphate), di-1-hexadecanyl phosphate (di-cetyl phosphate),di-cis-9-hexadecen-1-yl phosphate (di-plamitoleyl phosphate),di-1-octadecanyl phosphate (di-stearyl phosphate),di-cis-9-octadecen-1-yl phosphate (di-oleyl phosphate),di-trans-9-octadecen-1-yl phosphate (di-elaidyl phosphate),di-1-eicosanyl phosphate (di-arachidyl phosphate), di-1-docosanylphosphate (di-behenyl phosphate), 1-tetradecanyl sulfate (myristylsulfate), 1-hexadecanyl sulfate (cetyl sulfate), cis-9-hexadecen-1-ylsulfate (plamitoleyl sulfate), 1-octadecanyl sulfate (stearyl sulfate),cis-9-octadecen-1-yl sulfate (oleyl sulfate), trans-9-octadecen-1-ylsulfate (elaidyl sulfate), 1-eicosanyl sulfate (arachidyl sulfate), and1-docosanyl sulfate (behenyl sulfate).

Another category of emulsifiers includes, for example, glycerylmonostearate, glyceryl monopalmitate, glyceryl monooleate, etc.;monostearin, monopalmitin, monoolein, Lactic acid esters of mono- anddiglycerides of fatty acids, citric acid esters of mono- anddiglycerides of fatty acids, mono- and diacetyl tartaric acid esters ofmono- and diglycerides of fatty acids, sucrose esters of fatty acids,i.e., mono-, di- and triesters of sucrose with fatty acids.

A further category of emulsifiers includes fatty acid esters ofpropane-1,2-diol. Non-limiting examples include 1-hydroxypropan-2-yldodecanoate, 2-hydroxypropyl dodecanoate, propane-1,2-diyldidodecancoate, 1-hydroxypropan-2-yl tetradecanoate, 2-hydroxypropyltetradecanoate, propane-1,2-diyl ditetradecancoate, 1-hydroxypropan-2-ylhexadecanoate, 2-hydroxypropyl hexadecanoate, and propane-1,2-diyldihexadecancoate.

A still further category of emulsifiers includes C₈-C₁₈ alkylglycosideshaving the formula:CH₃(CH₂)_(q)O[G]_(p)Hwherein G represents a monosaccharide residue chosen from glucose,fructose, mannose, galactose, talose, allose, altrose, idose, arabinose,xylose, lyxose, ribose and mixtures thereof, the index p is from 1 to 4,the index q is from 7 to 17. The following are non-limiting examples ofalkyl glucoside surfactants include(2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-octooxyoxane-3,4,5-triol (octylglucoside, n-octyl-b-D-glucoside),(2R,3R,4S,5S,6R)-2-decoxy-6-(hydroxymethyl)tetra-hydropyran-3,4,5-triol(decyl glucoside, n-decyl-b-D-glucoside), and(2R,3R,4S,5S,6R)-2-dodecoxy-6-(hydroxymethyl)tetrahydropyran-3,4,5-triol(dodecyl glucoside, lauryl glucoside, n-dodecyl-b-D-glucoside). Oneexample of a suitable admixture of C₈-C₁₆ alkylglycosidyl nonionicsurfactants is PLANTACARE™ 818 UP available from Cogins Chemical Co.

A still another category of emulsifiers includes polyoxyethylene glycolalkyl ethers having the formula:RO(CH₂CH₂O)_(n)Hwherein R is a linear or branched alkyl group having from 6 to 20 carbonatoms and n is an integer of about 2 to about 20.

One example of suitable ethoxylate alcohols is the NEODOL™ ethoxylatedalcohols from Shell Chemicals. NEODOL™ 23-1 comprises a mixture of Runits that are C₁₂ and C₁₃ in length with an average of 1 ethoxy unit.Non-limiting examples of ethoxylated alcohols include NEODOL™ 23-1,NEODOL™ 23-2, NEODOL™ 23-6.5, NEODOL™ 25-3, NEODOL™ 25-5, NEODOL™ 25-7,NEODOL™ 25-9, PLURONIC™ 12R3, and PLURONIC™ 25R2 available from BASF.

In certain example embodiments, the emulsifier includes polyoxyethyleneglycol alkyl ethers having the formula:RO(CH₂CH(CH₃)O)_(n)Hwherein R is a linear or branched alkyl group having from 6 to 20 carbonatoms and n is an integer of about 2 to about 20.

In certain example embodiments, the emulsifier includes polyoxyethylenepolyoxypropylene block copolymers known as “poloxamers” having theformula:HO(CH₂CH₂)_(y1)(CH₂CH₂CH₂O)_(y2)(CH₂CH₂O)_(y3)OH.These are nonionic block copolymers composed of a polypropyleneoxy unitflanked by two polyethyleneoxy units. The indices y¹, y², and y³ havevalues such that the poloxamer has an average molecular weight of fromabout 1000 g/mol to about 20,000 g/mol. These are also well known by thetrade name PLURONICS™. These compounds are commonly named with the wordPoloxamer followed by a number to indicate the specific co-polymer, forexample Poloxamer 407 having two PEG blocks of about 101 units (y¹ andy³ each equal to 101) and a polypropylene block of about 56 units. Thiscategory of emulsifiers is commercially available, for example, underthe trade name LUTROL™ F-17 available from BASF.

A further example of emulsifiers includes alkyl amides that areethoxylate, propoxylated, or mixtures thereof, having the formula:

wherein R is C₇-C₂₁ linear alkyl, C₇-C₂₁ branched alkyl, C₇-C₂₁ linearalkenyl, C₇-C₂₁ branched alkenyl, and mixtures thereof. R¹ is ethylene;R² is C₃-C₄ linear alkylene, C₃-C₄ branched alkylene, and mixturesthereof; in some iterations R² is 1,2-propylene. Emulsifiers thatcomprise a mixture of R¹ and R² units can comprise from about 4 to about12 ethylene units in combination with from about 1 to about 41,2-propylene units. The units can be alternating or grouped together inany combination suitable to the formulator. In one iteration, the ratioof R¹ units to R² units is from about 4:1 to about 8:1. In anotheriteration, a R² unit (i.e., 1,2-propylene) is attached to the nitrogenatom followed by the balance of the chain comprising from 4 to 8ethylene units.

R³ is hydrogen, C₁-C₄ linear alkyl, C₃-C₄ branched alkyl, and mixturesthereof; preferably hydrogen or methyl, more preferably hydrogen.

R⁴ is hydrogen, C₁-C₄ linear alkyl, C₃-C₄ branched alkyl, and mixturesthereof. When the index m is equal to 2 the index n must be equal to 0and the R⁴ unit is absent and is instead replaced by a—[(R¹O)_(x)(R²O)_(y)R³] unit.

The index m is 1 or 2, the index n is 0 or 1, provided that when m isequal to 1, n is equal to 1; and when m is 2 n is 0; in one example, mis equal to 1 and n is equal to one, resulting in one—[(R¹O)_(x)(R²O)_(y)R³] unit and R⁴ being present on the nitrogen. Theindex x is from 0 to about 50, in one embodiment from about 3 to about25, in another embodiment x is from about 3 to about 10. The index y isfrom 0 to about 10, in one example y is 0; however, when the index y isnot equal to 0, y is from 1 to about 4. In one embodiment all of thealkyleneoxy units are ethyleneoxy units.

Surfactants

The disclosed emulsions can be further stabilized by the addition of oneor more surfactants and/or co-surfactants and/or emulsion stabilizers.Without wishing to be limited by theory, surfactants are believed toform an interfacial film between the oil and water phase of the emulsionthereby providing stability. The following are non-limiting examples ofsurfactants suitable for use in preparing the disclosed emulsions.

Alkyl Sulfates

The disclosed compositions can comprise one or more C₁₀-C₂₀ primary,branched chain and random alkyl sulfates having the formula ROSO₃Mwherein R is a linear or branched chain comprising from 10 to 20 carbonatoms and M represents a water soluble cation. Non-limiting examples ofalkyl sulfates suitable for use in the disclosed compositions includesodium decylsulfate, sodium dodecylsulfate, sodium tetradecylsulfate,sodium hexadecylsulfate, and sodium octadecylsulfate.

Alkyl Alkoxy Sulfates

The disclosed compositions can comprise one or more C₁₀-C₁₈ alkyl alkoxysulfates having the formula:CH₃(CH₂)_(x)(OCH₂CH₂)_(y)OSO₃M

wherein the index x is from 9 to 17, y is from 1 to 7 and M is a watersoluble cation chosen from ammonium, lithium, sodium, potassium andmixtures thereof. A non-limiting example includes sodium dodecyldiethoxy sulfate having the formula:CH₃(CH₂)₁₁(OCH₂CH₂)₂OSO₃Na.

Alkyl alkoxy sulfates are also commercially available as a mixture ofethoxylates, for example, sodium laureth sulfate is available as amixture of ethoxylates, i.e., the index y is from 2 to 4. Other suitableexamples include sodium laureth-2 sulfate having an average of 2ethoxylates and a C₁₂ linear alkyl chain. Sodium laureth-2 is availableas Texapon™ N 56 from Cognis Corp. Further examples of alkyl alkoxysulfates includes sodium laureth-1 sulfate, sodium laureth-3 sulfate,sodium laureth-4 sulfate, sodium myreth-2 sulfate and sodium myreth-3sulfate.

Alkenyl Sulfonates

The disclosed compositions can comprise one or more C₁₀-C₁₈ alkenylsulfonates (α-olefin sulfonates) having the formula:CH₃(CH₂)_(z)CH═CHSO₃M

wherein the index z is from 7 to 15 and M is a water soluble cationchosen from ammonium, lithium, sodium, potassium and mixtures thereof.Olefin sulfonates are commercially available as a mixture of alkenylchains, for example, sodium C₁₄-C₁₆ olefin sulfonate Bio-Terge™ AS-40available from Stepan. Further non-limiting examples of alkenylsulfonates include C₁₂-C₁₆ olefin sulfonates and C₁₄-C₁₈ olefinsulfonates. Another example is C₁₂-C₁₅ pareth-15 sulfonate available asAvanel™ S 150 CG.

Alkyl Alkoxy Carboxylates

The disclosed compositions can comprise one or more C₁₀-C₁₈ alkyl alkoxycarboxylates having the formula:CH₃(CH₂)_(x)(OCH₂CH₂)_(y)CO₂M

wherein the index x is from 9 to 17, y is from 1 to 5 and M is a watersoluble cation chosen from ammonium, lithium, sodium, potassium andmixtures thereof. A non-limiting example includes sodium dodecyldiethoxy carboxylate having the formula:CH₃(CH₂)₁₁(OCH₂CH₂)₂CO₂Na.

Alkyl alkoxy carboxylates are also commercially available as a mixtureof ethoxylates, for example, sodium laureth sulfate is available as amixture of ethoxylates, i.e., the index y is from 2 to 4. Other suitableexamples include sodium laureth-2 sulfate having an average of 2ethoxylates and a C₁₂ linear alkyl chain. Sodium laureth-2 is availableas Texapon™ N 56 from Cognis Corp. Further examples of alkyl alkoxysulfates include sodium laureth-1 sulfate, sodium laureth-3 sulfate,sodium laureth-4 sulfate, sodium myreth-2 sulfate and sodium myreth-3sulfate.

Isethionate Esters of Alkyl Alkoxy Carboxylic Acids

The disclosed compositions can comprise one or more C₁₀-C₁₈ isethionateesters of alkyl alkoxy carboxylates having the formula:CH₃(CH₂)_(x)(OCH₂CH₂)_(y)OCH₂C(O)OCH₂CH₂SO₃M

wherein the index x is from 9 to 17, the index y is from 1 to 5 and M isa water soluble cation. Isethionate esters of alkyl alkoxy carboxylatesare described in U.S. Pat. No. 5,466,396 the disclosure of which isincluded herein by reference in its entirety.

Alkyl Carboxyamides

The disclosed compositions can comprise one or more C₁₀-C₁₈ alkylcarboxyamides having the formula:CH₃(CH₂)_(x)C(O)NR(CH₂)_(y)CO₂M

wherein R is hydrogen or methyl the index x is from 9 to 17, the index yis from 1 to 5 and M is a water soluble cation. A non-limiting exampleof an alkyl carboxyamide suitable for use in the disclosed compositionsincludes potassium cocoyl glycinate available as AMILITE™ GCK-12 fromAjinomoto. A further example includes compounds wherein R is methyl, forexample, sodium cocoyl sarcosinate.

The following are non-limiting examples of zwitterionic surfactantssuitable for use in preparing the disclosed emulsions.

Alkyl Amide Betaines

One category of zwitterionic surfactants relates to C₁₀-C₁₆ alkyl amidebetaines having the formula:CH₃(CH₂)_(w)C(O)NH(CH₂)_(u)N⁺(CH₃)₂(CH₂)_(t)CO₂ ⁻

wherein the index w is from 9 to 15, the index u is from 1 to 5 and theindex t is from 1 to 5. Non-limiting examples of betaine surfactantsincludes {[3-(decanoylamino)ethyl]-(dimethyl)-ammonio}acetate,{[3-(decanoylamino)ethyl](dimethyl)ammonio}-acetate,{[3-(dodecanoyl-amino)ethyl](dimethyl)ammonio}acetate,{[3-(dodecanoylamino)propyl]-(dimethyl)-ammonio}acetate,{[3-(dodecanoylamino)-butyl](dimethyl)ammonio}acetate,{[3-(tetra-decanoylamino)ethyl](dimethyl)-ammonio}acetate,{[3-(tertadecanoylamino)-propyl](dimethyl)ammonio}acetate,{[3-(hexadecanoylamino)ethyl](dimethyl)-ammonio}acetate, and{[3-(hexa-decanoylamino)propyl](dimethyl)ammonio}acetate.

Alkyl Amide Sultaines

Another category of zwitterionic surfactants relates to C₁₀-C₁₆ alkylamide sultaines having the formula:CH₃(CH₂)_(w)C(O)NH(CH₂)_(u)N+(CH₃)₂(CH₂)_(t)SO₃ ⁻

wherein the index w is from 9 to 15, the index u is from 1 to 5 and theindex t is from 1 to 5. Non-limiting examples of sultaine surfactantsincludes {[3-(decanoylamino)ethyl]-(dimethyl)-ammonio}methanesulfonate,{[3-(decanoylamino)ethyl](dimethyl)ammonio}-methanesulfonate,{[3-(dodecanoyl-amino)ethyl](dimethyl)ammonio}methanesulfonate,{[3-(dodecanoylamino)-propyl](dimethyl)ammonio}methanesulfonate,{[3-(dodecanoyl-amino)butyl](dimethyl)-ammonio}methanesulfonate,{[3-(tetradecanoylamino)ethyl]-(dimethyl)ammonio}methanesulfonate,{[3-(tertadecanoylamino)propyl](dimethyl)-ammonio}methanesulfonate,{[3-(hexadecanoylamino)ethyl](dimethyl)ammonio}-methanesulfonate, and{[3-(hexadecanoylamino)propyl](dimethyl)ammonio}-methanesulfonate.

Alkyl Hydroxy Sultaines

A further category of zwitterionic surfactants relates to C₁₀-C₁₆ alkylhydroxy sultaines having the formula:CH₃(CH₂)_(w)N⁺(CH₃)₂CH₂CHOHCH₂SO₃ ⁻

wherein the index w is from 9 to 15. Non-limiting examples of alkylhydroxy sultaine surfactants includes3-[dodecyl(dimethyl)azaniumyl]-2-hydroxypropane-1-sulfonate (laurylhydroxysultaine),3-[tetradecyl(dimethyl)azaniumyl]-2-hydroxypropane-1-sulfonate (myristylhydroxysultaine),(Z)-{dimethyl[3-(octadec9-enamido)propyl]ammonio}-methanesulfonate(oleyl hydroxysultaine), and the like.

Carriers

Included within the components of the aqueous phase described herein arecarriers. In certain example embodiments, the disclosed aqueous phasecan comprise from about 0.01% to about 90% by weight of one or morecarriers.

In certain example embodiments, the aqueous phase can comprise fromabout 85% to about 99% by weight of water. In one embodiment, thecompositions comprise from about 85% to about 95% by weight of one ormore carriers. In one embodiment, water is the sole carrier. In afurther example, water comprises from about 87% to about 99% by weightof the carrier. In a still further examples water comprises from about90% to about 95% by weight of the carrier. In one embodiment the carriercan also comprise one or more alcohols. Non-limiting examples ofsuitable alcohols include ethanol, n-propanol, iso-propanol, andpropanediol. The formulator can, however, choose any mixture of watersoluble organic solvents and/or water.

In another example embodiment, disclosed herein is a process for formingan emulsion, comprising combining under high shear mixing:

a) a lipid component comprising:

-   -   i) less than about 15% by weight of d-α-tocopheryl polyethylene        glycol 1000 succinate (TPGS) or derivatives thereof, and    -   ii) at least one or more non-polar compounds; and        b) an aqueous component comprising:    -   i) less that about 15% by weight of one or more emulsifiers,    -   ii) one or more adjunct ingredients, and    -   iii) the balance one or more carriers;        wherein the emulsion comprises at least about 20% by weight of        the one or more non-polar compounds and wherein the emulsion        comprises lipid-component droplets having a mean particle size        or median particle size less than or equal to about 5 μm.        Additives

In certain example embodiments, the compositions provided herein caninclude one or more additives. For example, the compositions may includeone or more adjunct components or additives are also included, such asvitamins. The vitamins can be added directly, for example, tocopherol,or the vitamin can be added in a releasable form, for example, ascorbylpalmitate. Other suitable adjunct components include thickening agents,for example, starches, vegetable gums, pectin or proteins. Non-limitingexamples of thickening agents include alginic acid (E400), sodiumalginate (E401), potassium alginate (E402), ammonium alginate (E403),calcium alginate (E404), agar (E406), carrageenan (E407), locust beangum (E410) pectin (E440), gelatin (E441) and xanthan gum. Other adjunctcomponents or additives include essential oils, fragrances, flavorants,and colorants.

In certain example embodiments, the additives are added duringpreparation of aqueous phase as described herein. For example, polaradditives can be added to a polar carrier such as water. Thewater/additive mixture can then be included within the resultantcompositions when the aqueous phase is combined with the lipid phase asdescribed herein. In certain example embodiments, one or more additivesmay be added to the emulsion after the lipid phase is mixed with theaqueous phase as described herein. That is, the one or more additivescan be added to emulsion after the emulsion is prepared.

Compositions

In certain example embodiments, provided is an oil-in-water emulsioncomposition, such as an emulsion produced by the processes or methodsdescribed herein. For example, the emulsion can include a lipidcomponent, an emulsifier, a surfactant, as described herein. The lipidcomponent of the oil-in-water emulsion can be any nonpolar compound asdescribed herein, such as an omega fatty acid. For example, thecomposition can include omega-3 fatty acids, omega-5 fatty acids,omega-6 fatty acids, omega-7 fatty acids. In other example compositions,the oil is a flaxseed oil or other seed oil. The lipids, for example,can comprise a substantial amount of the total composition. For example,the lipids can comprise about 50%, 49%, 48%, 47%, 46%, 45%, 44%, 43%,42%, 41%, 40%, 39%, 38%, 37%, 36%, 35%, 34%, 33%, 32%, 31%, 30%, 29%,28%, 27%, 26%, 25%, 24%, 23%, 22%%, 21%, 20%, 19%, 18%, 17%, 16%, or 15%of the emulsion.

Additionally, the lipid component is present in small droplets or“particles” as described herein. The particles, for example, can be anysize described herein. As an example, the lipid particles of thecomposition have an average diameter of less than or equal to about 5μm. In certain example embodiments, the average diameter is less than orequal to 4.5 μm. In certain example embodiments, the average diameter isless than or equal to 4 μm. In a further example embodiment the averagediameter is less than or equal to 3.5 μm. In further embodiments theaverage diameter is less than or equal to 3 μm. In a yet anotherembodiment the average diameter is less than or equal to 2.5 μm. In astill yet further embodiment the average diameter is less than or equalto 2 μm. In a still yet another embodiment the average diameter is lessthan or equal to 1.5 μm. In a yet still further embodiment the averagediameter of the particles in the emulsion is less than or equal to about1 μm. In certain example embodiments, about 95%, 94%, 93%, 92%, 91%,90%, 89%, 88%, 87%, 86%, 85%, 84%, 83%, 82%, 81%, 80%, 79%, 78%, 77%,76%, 75%, 74%, 73%, 72%, 71%, 70%, 69%, 68%, 67%, 66%, 65%, 64%, 63%,62%, 61%, 60%, 59%, 58%, 57%, 56%, 55%, 54%, 53%, 52%, 51%, 50%, 49%,48%, 47%, 46%, 45%, 44%, 43%, 42%, 41%, 40%, 39%, 38%, 37%, 36%, or 35%of the lipid particles of the emulsion are less than about 5 μm, 4 μm, 3μm, 2 μm, or 1 μm in size.

In certain example embodiments, the emulsion composition can include anemulsifier. The emulsifier can be any of the emulsifiers describedherein. That is, the emulsifier can be any emulsifier identified hereinthat can, when used according to the methods and processes describedherein, provide the desired median or mean particle size of theresulting droplets. The emulsifier, for example, can be present in theemulsion in an amount that is less than about 10% of the emulsion, suchas about 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or 1% of the emulsion.

In certain example embodiments, the emulsion composition canadditionally include a surfactant. The surfactant can be any surfactantdescribed herein. Example surfactants include, for example, an alkylsulfate, alkyl alkoxy sulfate, alkenyl sulfonate, alkyl alkoxycarboxylate, isethionate esters of alkyl alkoxy carboxylic acids, alkylcarboxyamide, alkyl amide betaine, alkyl amide sultaine, or alkylhydroxy sultaine. In certain example embodiments, the surfactant isd-α-tocopheryl polyethylene glycol 1000 succinate (“TPGS”) or aderivative thereof. The surfactant is present in a low amount asdescribed herein. For example, the surfactant can comprise less thanabout 15%, 14%, 13%, 12%, 11%, 10%, 9%, 8%, 7%, 6%, 5%, 4%, 3%, 2%, or1% of the emulsion. In certain example embodiments, the compositions canalso include any of the carriers and/or additives as described herein.

The emulsion compositions described herein, such as a compositionproduced by the methods and processes described herein, can be used withand/or integrated into a variety of consumable products and foodstuffs.For example, the compositions provided herein can be used innutraceutical products, such as fish oil or flaxseed oil healthsupplements. The fish oil or flaxseed oil, for example, can be includedas the lipid component in the emulsion as described herein, and theprepared emulsion can be used a direct supplement. The prepared emulsioncan also include additives, for example, to enhance shelf-life, flavor,and product appearance. In certain example embodiments, the emulsioncompositions may be included within a pharmaceutical/nutraceuticaldeliver form, such as within a softgel.

Without wishing to be bound by any particular theory, and as thoseskilled in the art will appreciate, it is believed the small particlesize of the oil droplets in the compositions/products described hereinincrease absorption of the lipid component. For example, if the lipidcomponent of the lipid phase is fish oil, it is believed that thesmaller particle size will increase absorption of the fish oil when theemulsion is ingested. It is believed, for example, that the smallparticle size increases the rate of delivery and/or bioavailability ofthe fish oil when the fish oil is ingested, thereby increasing theabsorption of the consumed fish oil. In certain example embodiments, itis believed that use of the emulsion compositions provided herein willincrease absorption by 5%, 10%, 15%, 20%, 25%, 30%, 35%, 40%, 45%, 50%,55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 95%, 100% or more. Although anyconventional means may be used to determine absorption, in certainexample embodiments fatty acid analysis via gas chromatography (GC),and/or high performance liquid chromatography (HPLC), can be performedon a blood sample from a subject after the subject has consumed thecomposition.

EXAMPLES

The present invention is described in further detain in the followingexamples which are not in any way intended to limit the scope of theinvention as claimed. The following examples are offered to illustrate,but not to limit the claimed invention.

Example 1—Emulsification with 5% TPGS

To prepare a 1000 kg industrial batch of an example emulsion asdescribed herein, with 5% TPGS, a premix was prepared as the lipidcomponent. The premix was then mixed with an aqueous component, alongwith other components.

Preparation of Premix

To prepare the premix (340 kg), approximately 49.98 kg of TPGS (e.g.,Antares Vitamin E TPGS NF or other TPGS suppliers) were heated to 65° C.until it transitioned from a semisolid to a liquid form. Separately,290.02 kg of fish oil (Organic Technologies™) was weighed and thenheated to 40° C. in an industrial mixer. The liquid TPGS was added tothe heated fish oil. The mixer system was nitrogen flushed, and theTPGS-fish oil mixture was mixed for approximately 20 minutes (or untilthe mixture is a uniform consistency) to form a liquid premix. Thepremix is then ready to mix with the water phase, described below, orstored. In certain examples, the premix is stored before use, in whichcase the premix may return to a semi-solid phase. In such examples,before the premix is mixed with the water phase (as described below),the semi-solid phase premix is heated to approximately 40° C. for about15 min in order to convert the semi-solid phase premix back to a liquidphase. The components of the premix are shown in Table 1.

TABLE 1 Components of Premix. Component Percentage Fish Oil 85.3% TPGS14.7% TOTAL BATCH 100.00%Preparation of Aqueous Phase with Emulsifier

To prepare the water phase 312 kg of room-temperature water (roughly 0.3liters) was placed into the holding tank of a high shear Ross™HSM-405SC-25 mixer and thereafter allowed to flow through the mixingchamber of the high shear mixer. Separately, 36.0 kg of powderedemulsifier (e.g., Blue Pacific™, Tic Tim, and/or CNI™ blend) was placedinto the funnel tank of the high shear mixer. Additionally, 180 kgxylitol, 0.5 kg sorbic acid, 4 kg citric acid, 6 kg Grape Color, 35 kgmixed berry flavor, 0.3 kg rosemary extract, 85 kg glycerin, 1.0 kgxanthan easy, and 0.2 kg ascorbyl palmitate were weighed. The xanthaneasy and ascorbyl palmitate were added to the funnel of the Ross mixer,(along with the emulsifier, see above). The glycerin was then added tothe water in the holding tank of the mixer. The mixer was then run at65% max speed for about 5 minutes to mix the water and glycerin. Thexylitol, sorbic acid, citric acid, strawberry color, passion-pineappleflavor, mixed tocopherol, and rosemary extract are then added to thewater-glycerin mixture, and the combination is mixed for an additional3-5 minutes at 65% power. The power on the Ross mixer was adjusted to100% (approximately 3,600 rpm), and the funnel valve of the Ross mixerwas fully opened to allow its contents to quickly flow in to the holdingtank of the mixer. After the contents of the funnel were emptied in tothe holding tank, the funnel valve was closed and mixing continues forabout 5 minutes.

Preparation of Oil in Water Phase Including 5% TPGs

To prepare the final emulsified product, 340 kg of premix was slowly fedinto the high shear mixer system through an intake valve of the mixer.When using a Ross mixer, for example, the T-valve valve remainsapproximately 70% closed (i.e., about ¼ open), thus allowing slow inputof the premix into the water phase. The premix was then mixed with thewater phase in the high shear mixer for approximately 25-30 minutes. Theemulsified product included the components shown in Table 2, with thefinal product including approximately 29% fish oil and 5% TPGS.

TABLE 2 Components of 5% TPGS emulsification Component Percentage Water31.2% Grape Color No. 03039 0.6% Sorbic Acid 0.05% Xylitol 18.0% CitricAcid 0.40% Glycerin 8.5% Emulsifier 3.6% Xanthan Easy 0.10% AscorbylPalmitate 0.02% Mixed Berry Flavor 3.5% Rosemary Extract 0.03% Premix34.000% (29% Fish Oil, 5% TPGS in final product) TOTAL BATCH 100.00%

Following preparation of the emulsified product, a sample of the productwas subjected to particle size analysis to determine the size of thenon-polar (oil) component droplets within the sample. Briefly, particlesize analysis was conducted using a Malvern® MasterSizer 2000 LASERdiffractor. As those skilled in the art will appreciate, the Malvern®MasterSizer LASER diffractor is considered an ensemble analyzer thatcalculates a volume distribution from the LASER (Light Amplification byStimulated Emission of Radiation) diffraction pattern of a suspension ofparticles. The raw scatter data are then processed using themanufacturer's algorithm and presented on the basis of EQUIVALENTSPHERICAL DIAMETER.

For the sample of the emulsified product using 5% TPGS in the finalproduct, 90% of the particles (D(0.9)) had a size less than 1.088 μm,while 50% of the particles (D(0.5)) had a size smaller than 0.677 km.Further, 10% of the particles (D(0.1)) had a size smaller than 0.390 μm.The mean particle size (volume weighted mean) was 0.713 km. A histogramof particle size distribution for the 5% TPGS emulsification sample isshown in FIG. 1.

Example 2—Emulsification with 3% TPGS

In this example, an emulsification was prepared as described in Example1, except that the final emulsification contained 3% TPGS. Briefly, thepremix was prepared as described in Example 1, with the TPGS comprising9.41% of the premix and the fish oil comprising the remaining 90.59% ofthe premix. Following preparation of the emulsification, the finalemulsified product included the components shown in Table 3. Further,when 9.41% TPGS was used in the premix, the final emulsion contained28.88% fish oil and 3% TPGS.

TABLE 3 Components of 3% TPGS emulsification Component Percentage Water35.82%  Grape Color No. 03039  0.6% Sorbic Acid 0.05% Xylitol 17.0%Citric Acid 0.40% Glycerin   7% Emulsifier 3.60% Xanthan Easy 0.10%Ascorbyl Palmitate 0.02% Mixed Berry Flavor  3.5% Rosemary Extract 0.03%Premix 31.88% (28.88% fish oil, 3% TPGS in final product) TOTAL BATCH100.00% 

After preparation of the 3% TPGS emulsified product, a sample of theproduct was subjected to particle size analysis as described in Example1 to determine the size of the non-polar (oil) component droplets withinthe sample. With 3% TPGS in the final emulsification, 90% of theparticles (D(0.9)) had a size less than 1.490 μm, while 50% of theparticles (D(0.5)) had a size smaller than 0.974 km. Further, 10% of theparticles (D(0.1)) had a size smaller than 0.614 μm. The mean particlesize (volume weighted mean) was 1.019 km. A histogram of the particlesize distribution for the 3% TPGS emulsification is shown in FIG. 2.

Example 3—Emulsification with 1% TPGS

In this example, an emulsification was prepared as described in Example1, except that the final emulsification contained 1% TPGS. Briefly, thepremix was prepared as described in Example 1, with the TPGS comprising3.35% of the premix and the fish oil comprising the remaining 96.65% ofthe premix. Following preparation of the emulsification, the finalemulsified product included the components shown in Table 4. Further,when 3.35% TPGS was used in the premix, the final emulsion contained28.88% fish oil and 1% TPGS.

TABLE 4 Components of 1% TPGS emulsification Component Percentage Water37.82% Grape Color No. 03039  0.6% Sorbic Acid 0.050% Xylitol   17%Citric Acid 0.400% Glycerin    7% Emulsifier 3.600% Xanthan Easy 0.100%Ascorbyl Palmitate  0.02% Mixed Berry Flavor  3.5% Rosemary Extract 0.03% Premix 29.88% (28.88% fish oil, 1% TPGS in final product) TOTALBATCH 100.00% 

After preparation of the 1% TPGS emulsified product, a sample of theproduct was subjected to particle size analysis as described in Example1 to determine the size of the non-polar (oil) component droplets withinthe sample. Initially, the droplets displayed a bi-modal distribution,with peaks around 0.1 μm and 1.7 μm (data not shown). Nevertheless, the90% of the particles (D(0.90)) were less than 2.116 μm in diameter. Whenthe sample was repeat tested, however, a single peak was observed around1.7 μm. More particularly, with the repeat test with 1% TPGS in thefinal emulsification, 90% of the particles (D(0.9)) had a size less than2.466 μm, while 50% of the particles (D(0.5)) had a size smaller than1.664 μm. Further, 10% of the particles (D(0.1)) had a particle sizesmaller than 1.163 μm. The mean particle size (volume weighted mean) was1.753 km. A histogram of particle size distribution for the 1% TPGSemulsification (repeat) is shown in FIG. 3.

Example 4—Emulsification with 0.5% TPGS

In this example, an emulsification was prepared as described in Example1, except that the final emulsification contained 0.5% TPGS. Briefly,the premix was prepared as described in Example 1, with the TPGScomprising 2.13% of the premix and the fish oil comprising the remaining97.87% of the premix. Following preparation of the emulsification, thefinal emulsified product included the components shown in Table 5.Further, when 2.13% TPGS was used in the premix, the final emulsioncontained 23% fish oil and 0.5% TPGS.

TABLE 5 Components of 0.5% TPGS emulsification Component PercentageWater 41.7% Grape Color No. 03039 0.6% Sorbic Acid 0.050% Xylitol18.000% Citric Acid 0.400% Glycerin 8.5% Emulsifier 3.600% Xanthan Easy0.100% Ascorbyl Palmitate 0.020% Mixed Berry Flavor 3.5% RosemaryExtract 0.03% Premix 23.5% (23% fish oil, 0.5% TPGS in final product)TOTAL BATCH 100.00%

After preparation of the 0.5% TPGS emulsified product, a sample of theproduct was subjected to particle size analysis as described in Example1 to determine the size of the non-polar (oil) component droplets withinthe sample. With 0.5% TPGS in the final emulsification, 90% of theparticles (D(0.9)) had a size less than 3.617 μm, while 50% of theparticles (D(0.5)) had a size smaller than 2.413 km. Further, 10% of theparticles (D(0.1)) had a particle size smaller than 1.707 μm. The meanparticle size (volume weighted mean) was 2.570 km. A histogram ofparticle size distribution for the 0.5% TPGS emulsification sample isshown in FIG. 4.

Example 5—Emulsification with 0.3% TPGS

In this example, an emulsification was prepared as described in Example1, except that the final emulsification contained 0.3% TPGS. Briefly,the premix was prepared as described in Example 1, with the TPGScomprising 1.35% of the premix and the fish oil comprising the remaining98.65% of the premix. Following preparation of the emulsification, thefinal emulsified product included the components shown in Table 6.Further, when 1.35% TPGS was used in the premix, the final emulsioncontained 22.8% fish oil and 0.3% TPGS.

TABLE 6 Components of 0.3% TPGS emulsification Component PercentageWater 36.700% Grape Color No. 03039 0.600% Sorbic Acid 0.050% Xylitol19.000% Citric Acid 0.400% Glycerin 12.000% Emulsifier 4.500% XanthanEasy 0.100% Ascorbyl Palmitate 0.020% Flavor Passion-Pineapple 3.500%Rosemary Extract 0.030% Premix 23.100% (fish oil 22.8%, TPGS 0.3% infinal product) TOTAL BATCH 100.000%

After preparation of the 0.3% TPGS emulsified product, a sample of theproduct was subjected to particle size analysis as described in Example1 to determine the size of the non-polar (oil) component droplets withinthe sample. With 0.3% TPGS in the final emulsification, 90% of theparticles (D(0.9)) had a size less than 3.177 μm, while 50% of theparticles (D(0.5)) had a size smaller than 2.096 km. Further, 10% of theparticles (D(0.1)) had a particle size smaller than 1.449 μm. The meanparticle size (volume weighted mean) was 2.226 μm. A histogram ofparticle size distribution for the 0.3% TPGS emulsification sample isshown in FIG. 5.

Example 6—Sample without TPGS

As a comparison to Examples 1-5, in which TPGS was used in the premix,this example examined particle size of the non-polar (oil) componentdroplets in the absence of TPGS in the premix. Briefly, a mixture wasprepared as described in Example 1, expect that no TPGS was added to thepremix. That is, the “premix” component included only fish oil.Following the emulsification steps of Example 1, the final mixtureincluded the components shown in Table 7.

TABLE 7 Fish oil product without TPGS Component Percentage Water 26.290%Grape Color No. 03039 0.600% Sorbic Acid 0.050% Xylitol 18.000% CitricAcid 0.400% Glycerin 8.5000% Emulsifier 3.600% Xanthan Easy 0.100%Ascorbyl Palmitate 0.020% Flavor Passion-Pineapple 3.500% RosemaryExtract 0.030% Mixed tocopherol 0.910% Premix (fish oil alone) 38.000%TOTAL BATCH 100.00%

After preparation of the mixture without TPGS, a sample of the mixturewas subjected to particle size analysis as described in Example 1 todetermine the size of the non-polar (oil) component droplets within thesample. In the absence of TPGS, 90% of the particles (D(0.9)) had aparticle size less than 11.349 μm, while 50% of the particles (D(0.5))had a size smaller than 7.017 μm. Only less than 10% of the particles(D(0.1)) had a particle size smaller than 4.241 μm. The mean particlesize (volume weighted mean) was 7.470 μm. A histogram of particle sizedistribution for the sample without TPGS is shown in FIG. 6. Compared toExamples 1-5, which included TPGS in the premix, the absence of TPGS inthe premix resulted in a substantially larger mean and median particlesize of the non-polar (oil) component droplets.

DISCUSSION

Based on these data, the use of TPGS with the methods and systems asdescribed can substantially reduce the particle size of oil dropletswithin the emulsion. Likewise, a higher percentage of TPGS was generallycorrelated with a smaller particle size (the exception being 0.3 TPGS).Nonetheless, as compared with no TPGS, use of TPGS according to themethods and systems described herein resulted in substantially reducingthe particle size of the oil particles. For example, the mean particlesize with 5% TPGS in the final product sample was 0.713 km. In sharpcontrast, the mean particle size without TPGS in the premix was 7.470km. Hence, use of 5% TPGS for the final emulsion product, in accordancewith the methods and systems described herein, resulted in greater thana 10-fold decrease in particle size of the lipid (oil) component in theemulsion.

In view of the many possible embodiments to which the principles of thedisclosed invention may be applied, it should be recognized that theillustrated example embodiments are only preferred examples of theinvention and should not be taken as limiting the scope of theinvention. Rather, the scope of the invention is defined by thefollowing claims. We therefore claim as our invention all that comeswithin the scope and spirit of these claims.

The invention claimed is:
 1. An emulsion, comprising: a) water and/orother carrier; b) an emulsifier, wherein the emulsifier is present in anamount of about 15% or less by weight of the emulsion; c) d-α-tocopherylpolyethylene glycol succinate (“TPGS”) or a derivative thereof, whereinthe TPGS or derivative thereof is present in an amount less than 2% byweight of the emulsion; and d) at least 20% by weight of one or morelipids, wherein the lipids are present in the emulsion as dropletshaving a median particle size of greater than 1 μm but less than orequal to about 5 μm.
 2. The emulsion of claim 1, wherein the lipiddroplets have a median particle size of 1 μm to about 3 μm.
 3. Theemulsion of claim 1, wherein the emulsion comprises between about 30% toabout 50% by weight of the one or more lipids.
 4. The emulsion of claim1, wherein the emulsion comprises about 10% of the emulsifier.
 5. Theemulsion of claim 1, wherein the TPGS comprises less than 1.5% by weightof the emulsion.
 6. The emulsion of claim 5, wherein the TPGS comprisesless than 1% by weight of the emulsion.
 7. The emulsion of claim 6,wherein the TPGS comprises about 0.15% by weight of the emulsion.
 8. Theemulsion of claim 1, wherein the emulsion comprises about 20% to about50% by weight of the one or more lipids.
 9. The emulsion of claim 1,wherein the emulsifier is a water-soluble emulsifier.
 10. The emulsionof claim 1, wherein the TPGS is present in an amount greater than 0.1%but less than 2% by weight of the emulsion.
 11. A method for forming anemulsion, comprising: providing an oil phase, the oil phase comprisingd-α-tocopheryl polyethylene glycol succinate (“TPGS”) or one or morederivatives thereof and one or more non-polar compounds; providing anaqueous phase, wherein the aqueous phase comprises one or moreemulsifiers, and combining, under high-shear mixing, the oil phase andthe aqueous phase to form the emulsion, wherein the emulsion comprises(a) TPGS or a derivative thereof that is present in an amount less than2% by weight of the emulsion, (b) at least 20% by weight of the one ormore non-polar compounds, and wherein (c) the one or more emulsifiersare is present in an amount of about 15% or less by weight of theemulsion and wherein the non-polar compounds of the emulsion are presentas droplets having a median particle size greater than 1 μm but lessthan or equal to 5 μm.
 12. The method of claim 11, wherein the emulsioncomprises less than about 1% by weight TPGS or derivatives thereof. 13.The method of claim 11, wherein the TPGS comprises about 0.15% by weightof the emulsion.
 14. The method of claim 11, wherein the aqueous phasecomprises less than about 10% by weight of the one or more emulsifiers.15. The method of claim 11, wherein the non-polar droplets of theemulsion have a median particle size of greater than 1 μm to about 3 μm.16. The method of claim 11, wherein the emulsion comprises about 30% toabout 50% by weight of the one or more non-polar compounds.
 17. Themethod of claim 11, wherein the emulsion comprises about 35% to about45% by weight of the one or more non-polar compounds.
 18. The method ofclaim 11, wherein combining the oil phase and the aqueous phase underhigh-shear mixing comprises mixing the oil phase and the aqueous phasetogether while subjecting the mixture to a rotor speed of at least 2,000rounds per minute (rpm).
 19. The method of claim 11, wherein the oilphase and the aqueous phase are combined at ambient temperature.
 20. Themethod of claim 11, wherein the emulsion comprises about 20% to about50% by weight of the one or more lipids.
 21. The method of claim 11,wherein the one or more emulsifiers are a water-soluble emulsifier. 22.The method of claim 11, wherein the TPGS is present in an amount greaterthan 0.1% but less than 2% by weight of the emulsion.